Coastal: A Phase 3 Study of the PI3Kδ Inhibitor Zandelisib with Rituximab (R) Versus Immunochemotherapy in Patients with Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.2430-2430
• Main Authors: Jurczak, Wojciech, Zinzani, Pier Luigi Luigi, Cunningham, David, Azoulay, Michel, Huang, Wenying, Xu, Weiming, Ribrag, Vincent
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-148015

Background: Patients (pts) with iNHL treated with front-line immunochemotherapy may benefit from an alternative, chemotherapy-free regimen at relapse. Zandelisib, a potent, selective, and structurally differentiated oral PI3Kδ inhibitor is administered using a unique schedule consisting of 60 mg given daily over the first two 28-day cycles for response induction followed by Days 1-7 only of each subsequent cycle as maintenance therapy, with the treatment-free intervals intended for regulatory T-cells repopulation and mitigation of delayed immune-related toxicities. In a phase 1 study, zandelisib achieved an 87% response rate, with median duration of response not reached in patient with relapsed iNHL when given as a monotherapy or in combination with R. A low rate (< 10%) of Grade ≥ 3 immune-mediated adverse events of special interest associated with PI3kδ inhibitors was also observed in patients administered zandelisib (JCO 2020 38:15_suppl, 8016). An open-label, phase 2 study (TIDAL, NCT03768505) of zandelisib as monotherapy is ongoing in pts with relapsed/refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL). Methods: The COASTAL study is a randomized, open-label, controlled multicenter phase 3 trial to investigate the safety and efficacy of zandelisib in combination with R versus standard immunochemotherapy in pts with relapsed or refractory FL or MZL who received ≥1 prior lines of therapy. Eligible pts must have received an anti-CD20 antibody in combination with chemotherapy or lenalidomide (L); at least one bi-dimensionally measured lesion > 1.5 cm; adequate bone marrow, renal and hepatic function; ECOG performance status score of 0 to 1. Key exclusion criteria include: histologically confirmed diagnosis of FL grade 3b or transformed disease; administration of 2 prior immunochemotherapy regimens; prior PI3K inhibitor therapy; known lymphomatous involvement of the central nervous system. Subjects are randomized 1:1 to receive R-zandelisib or immunochemotherapy (R-CHOP or R-B) and stratified by type and number of prior treatment regimens, histology, and duration of treatment-free interval after last therapy. Zandelisib will be given for a duration of 2 years. Rituximab or immunochemotherapy will be given for a total of 6 cycles. Disease response will be assessed by an Independent Response Review Committee according to the modified Lugano Classification. Radiographic tumor assessment will be performed approximately every 12 weeks for the f